Methotrexate is a folate antagonist which has been used in cancer chemotherapy, in the treatment of psoriasis and as an antibacterial and antiprotozoal agent. A major side effect of methotrexate administration is the formation of a fatty liver and eventual cirrhosis. This has limited the general use of this drug. Most of the information concerning the toxicity of this drug has been obtained from clinical studies on human patients. No in depth studies have been conducted on experimental animals. A research proposal is outlined that will investigate the methotrexate induced liver injury in rats in order to establish a model with which the administration of this drug can be better correlated with liver injury. Little information is available concerning the biochemical mechanism in the liver responsible for these observed side effects. Methotrexate, which is an inhibitor of dihydrofolic reductase, depresses the synthesis of tetrahydrofolate coenzymes and hence one-carbon transfers are impaired. Since these coenzymes play a key role in methyl group genesis, this raises the possibility of impaired choline biosynthesis in the liver. Experiments will be conducted to test this postulation and relate this as a possible contributing factor to the observed liver damage. This research will also investigate various agents and factors that may counteract the side effects of methotrexate. It is hoped that these studies will increase the effective usage of methotrexate both as an anti-cancer drug and antipsoriatic agent by counteracting adverse side effects of methotrexate in the liver.